Headache Centre, Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy.
Advanced MRI Neuroimaging Centre, Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy.
Int J Mol Sci. 2023 Jul 31;24(15):12268. doi: 10.3390/ijms241512268.
Migraine is a debilitating neurological condition affecting millions of people worldwide. Until a few years ago, preventive migraine treatments were based on molecules with pleiotropic targets, developed for other indications, and discovered by serendipity to be effective in migraine prevention, although often burdened by tolerability issues leading to low adherence. However, the progresses in unravelling the migraine pathophysiology allowed identifying novel putative targets as calcitonin gene-related peptide (CGRP). Nevertheless, despite the revolution brought by CGRP monoclonal antibodies and gepants, a significant percentage of patients still remains burdened by an unsatisfactory response, suggesting that other pathways may play a critical role, with an extent of involvement varying among different migraine patients. Specifically, neuropeptides of the CGRP family, such as adrenomedullin and amylin; molecules of the secretin family, such as pituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal peptide (VIP); receptors, such as transient receptor potential (TRP) channels; intracellular downstream determinants, such as potassium channels, but also the opioid system and the purinergic pathway, have been suggested to be involved in migraine pathophysiology. The present review provides an overview of these pathways, highlighting, based on preclinical and clinical evidence, as well as provocative studies, their potential role as future targets for migraine preventive treatment.
偏头痛是一种影响全球数百万人的使人虚弱的神经系统疾病。直到几年前，预防性偏头痛治疗方法都是基于具有多效靶点的分子，这些分子针对其他适应症开发，通过偶然发现对偏头痛预防有效，尽管它们常常因耐受性问题导致低依从性而受到困扰。然而，对偏头痛病理生理学的研究进展使得人们能够确定新的潜在靶点，如降钙素基因相关肽（CGRP）。然而，尽管 CGRP 单克隆抗体和 gepants 带来了革命，但仍有相当一部分患者的反应仍不令人满意，这表明其他途径可能发挥关键作用，其在不同偏头痛患者中的参与程度各不相同。具体而言，CGRP 家族的神经肽，如肾上腺髓质素和胰岛淀粉样多肽；分泌素家族的分子，如垂体腺苷酸环化酶激活肽（PACAP）和血管活性肠肽（VIP）；受体，如瞬时受体电位（TRP）通道；细胞内下游决定因素，如钾通道，以及阿片系统和嘌呤能途径，都被认为与偏头痛的病理生理学有关。本文综述了这些途径，根据临床前和临床证据以及刺激性研究，强调了它们作为偏头痛预防治疗未来靶点的潜在作用。
